Acute hyperglycemia in uterine arteries from pregnant, but not non-pregnant mice, enhances endothelium-dependent relaxation

Chirayath, Haiju H.; Wareing, Mark; Taggart, Michael J.; Baker, Philip N.

doi:10.1016/j.vph.2006.09.001

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…5 Recent work from our laboratory assessed the effects of glucose on uterine artery contraction and relaxation. 6 Here, uterine arteries from pregnant animals showed increased contraction and a greater capacity to relax when exposed to increased glucose; this phenomenon was not observed in nonpregnant mice. Together, these studies provide evidence for altered vascular function in pregnant mice, to permit enhanced uterine, and hence placental, perfusion through gestation.…”

Section: Introductionmentioning

confidence: 75%

“…Main UL contraction to PE has been previously reported. 5,6 Furthermore, endothelial-dependent relaxation of ULs was enhanced in pregnant compared to nonpregnant controls. These data suggest that unique alterations of vascular function occur during pregnancy in the mouse and these changes facilitate optimal blood supply to the placental units.…”

Section: Discussionmentioning

confidence: 97%

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In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

et al. 2009

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Adequate blood flow provision through alterations in maternal vascular function is essential during pregnancy for optimal fetal development. Abnormal uterine vasculature adaptation, resulting in aberrant blood flow to the placenta, has been implicated as a possible cause of fetal growth restriction (FGR). Our study aimed to develop strategies to evaluate murine vascular function in pregnancy using wire myography. Main uterine artery loop and branch vessels isolated from near-term pregnant mice showed significant contraction to phenylephrine (PE). Endothelial-dependent relaxation was noted with acetylcholine (ACH). U46619 elicited significant contraction of umbilical arteries and veins, but relaxation was only demonstrable with the nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, our data suggest that murine uteroplacental and fetoplacental arteries show distinct responses to vasoactive agents. Furthermore, this study indicates that wire myography represents a robust technique for the assessment of murine uteroplacental and fetoplacental vascular function, which will aid evaluation of mouse genetic models of FGR.

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Section: Introductionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 97%

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

et al. 2009

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“…In the mouse, Cooke and Davidge showed increased endothelial-dependent vasodilation in uterine and mesenteric arteries in pregnancy (11). In addition, several studies in rats and guinea pigs have also found a decreased sensitivity to PE and an increased sensitivity to ME in uterine and mesenteric arteries (13,22,26,35,41,53), although one study showed an increased sensitivity to PE in uterine arteries (8). In our studies in the uninfected mouse, however, no significant differences in PE or ME responses were found when LP were compared with NP mice in either mesentery or uterine arteries.…”

Section: Discussionmentioning

confidence: 99%

Impaired vascular function in mice with an active cytomegalovirus infection

Gombos

Wolan²,

McDonald³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Human cytomegalovirus (CMV) is implicated in vascular complications through endothelial dysfunction. However, the effect of in vivo infections on vascular function in isolated arteries has not been examined. In pregnancy, systemic and uterine vascular adaptations accommodate increased blood volume through several mechanisms, including decreased sensitivity to vasoconstrictors and increased production of endothelial-dependent vasodilators. We hypothesized that an active in vivo CMV infection would reduce vasodilation of isolated arteries to the endothelial-dependent vasodilator methacholine and increase vasoconstriction to the alpha(1)-adrenergic receptor agonist phenylephrine and that these CMV-induced changes would be accentuated in late pregnancy. A mouse CMV infection model was used to study vascular responses in isolated mesenteric and uterine arteries from nonpregnant and late pregnant mice. In the mouse, CMV is not transmitted to the fetus. Accordingly, there was no evidence of active infection in any fetus examined, even though an active infection was found in salivary glands, uterine and mesenteric arteries, and placentas. Contrary to our hypothesis, increased endothelial-dependent vasodilation was found in mesenteric arteries from infected compared with uninfected nonpregnant and pregnant mice These data implicate active CMV infections in hypotensive disorders. Similarly, increased vasodilation was found in uterine arteries from infected vs. uninfected nonpregnant mice. However, this was completely reversed in infected compared with uninfected late pregnant mice in which vasodilation in uterine arteries was significantly reduced. Uterine arteries from infected pregnant mice also showed increased vasoconstriction to phenylephrine. Maternal infection led to decreased placental weights but had no effect on fetal weights in late pregnancy. These novel data demonstrate abnormal systemic and uterine vascular responses during an active CMV infection in both nonpregnant and late pregnant mice. Importantly, despite reduced placental weights, fetal weights were maintained, suggesting effective intrauterine compensation in the mouse model.

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“…However, experimental studies of hyperglycemia-evoked vascular effects have produced conflicting results. Acute treatment of cerebral or uterine arteries with high glucose was associated with enhanced endotheliumdependent vasodilation (15,17 Accumulating data have indicated that hyperglycemia-induced endothelial mitochondrial overproduction of ROS in microvasculature activates a number of intracellular pathways resulting in impaired endothelial function (31). One of these mechanisms is enhanced generation of diacylglycerol (DAG) and excessive PKC activation, which is a well-characterized cause of endothelial dysfunction in humans and animals with diabetes (30,31).…”

Section: H942mentioning

confidence: 99%

Role of impaired endothelial cell Ca²⁺signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy

Gokina

Bonev

Gokin

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Gokina NI, Bonev AD, Gokin AP, Goloman G. Role of impaired endothelial cell Ca 2ϩ signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy. Am J Physiol Heart Circ Physiol 304: H935-H945, 2013. First published February 1, 2013 doi:10.1152/ajpheart.00513.2012.-Diabetes mellitus in pregnancy is associated with impaired endothelium-mediated dilatation of maternal arteries, although the underlying cellular mechanisms remain unknown. In this study, we hypothesized that diabetes during rat gestation attenuates agonist-induced uterine vasodilation through reduced endothelial cell (EC) Ca 2ϩ elevations and impaired smooth muscle cell (SMC) hyperpolarization and SMC intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) responses. Diabetes was induced by an injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with a citrate buffer. Fura-2-based measurements of SMC [Ca 2ϩ ]i or microelectrode recordings of SMC membrane potential were performed concurrently with dilator responses to ACh in uteroplacental arteries from control and diabetic pregnant rats. ]i elevations were significantly reduced by diabetes. In conclusion, these data demonstrate that reduced endothelium-mediated hyperpolarization contributes to attenuated uteroplacental vasodilation and SMC [Ca 2ϩ ]i responses to ACh in diabetic pregnancy. Impaired endothelial Ca 2ϩ signaling is in part responsible for endothelial dysfunction in the uterine resistance vasculature of diabetic rats. Pharmacological improvement of EC Ca 2ϩ handling may provide an important strategy for the restoration of endothelial function and enhancement of maternal blood flow in human pregnancies complicated by diabetes. endothelial dysfunction; acetylcholine-induced hyperpolarization; fura-2; calcium signaling; pressurized arteries DIABETES MELLITUS is one of the most common medical complications of pregnancy that significantly contributes to maternal and perinatal morbidity and mortality (5,7,11,13,44). The worldwide rise in obesity among women of childbearing age is in part responsible for the increased prevalence of diabetes during pregnancy (44, 47). Pregestational and gestational diabetes are serious complications with short-and long-term consequences for both offspring and mothers. Despite the improvement in perinatal outcome in well-controlled diabetic pregnancies, problems related to abnormal fetal growth, stillbirth, and congenital malformations persist (13). Women with gestational and especially pregestational diabetes are also at higher risk for the development of hypertension and preeclampsia during pregnancy (5,10,60,61,68).Human diabetic pregnancy is associated with an increased vascular resistance in the maternal uteroplacental circulation. The prevalence of an abnormal uterine artery Doppler velocity waveform is much higher in diabetic than nondiabetic populations (6, 9, 39, 59). The strongest correlation between abnormal uterine artery Doppler waveform and adverse ...

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Acute hyperglycemia in uterine arteries from pregnant, but not non-pregnant mice, enhances endothelium-dependent relaxation

Cited by 4 publications

References 33 publications

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

Impaired vascular function in mice with an active cytomegalovirus infection

Role of impaired endothelial cell Ca²⁺signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy

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Acute hyperglycemia in uterine arteries from pregnant, but not non-pregnant mice, enhances endothelium-dependent relaxation

Cited by 4 publications

References 33 publications

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

Impaired vascular function in mice with an active cytomegalovirus infection

Role of impaired endothelial cell Ca2+signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy

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Role of impaired endothelial cell Ca²⁺signaling in uteroplacental vascular dysfunction during diabetic rat pregnancy